Mathematical modeling predicts that increased hsv-2 shedding in HIV-1 infected persons is due to poor immunologic control in ganglia and genital mucosa

Joshua T. Schiffer, David A. Swan, Amalia Magaret, Timothy W. Schacker, Anna Wald, Lawrence Corey

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


A signature feature of HIV infection is poor control of herpes virus infections, which reactivate from latency and cause opportunistic infections. While the general mechanism underlying this observation is deficient CD4+T-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether CD4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic responses. Here we compare genital shedding patterns of herpes simplex virus-2 (HSV-2) in 98 HIV infected and 98 HIV uninfected men matched on length of infection, HSV-1 serostatus and nationality. We demonstrate that high copy HSV-2 shedding is more frequent in HIV positive men, particularly in participants with CD4+ T-cell count <200/ L. Genital shedding is more frequent due to higher rate of shedding episodes, as well as a higher proportion of prolonged shedding episodes. eak episode viral load was not found to differ between HIV infected and uninfected participants regardless of CD4+ T-cell count. We simulate a mathematical model which recapitulates these findings and identifies that rate of HSV-2 release from neural tissue increases, duration of mucosal cytolytic immune protection decreases, and cell-free viral lifespan increases in HIV infected participants. These results suggest that increased HSV-2 shedding in HIV infected persons may be caused by impaired immune function in both latent and lytic tissue compartments, with deficits in clearance of HSV-2 infected cells and extracellular virus.

Original languageEnglish (US)
Article numbere0155124
JournalPloS one
Issue number6
StatePublished - Jun 2016

Bibliographical note

Funding Information:
AM received consulting fees from Immune Design and AiCuris. LC sits on the scientific advisory board for and holds stock (>1% of company) in Immune Design Corp. AW received consulting fees from Aicuris, Amgen, and grant support through her institution from Agenus, Genentech, Genocea, Gilead, and Vical. LC holds the following two patents: 1. Koelle DM, Chen H, Corey L. Immunologically significant herpes simplex virus antigens and methods for identifying and using same. US Patent 6,962,709. November 8, 2005. Hosken, McGowan, Fling, Posavad removed from inventorship via Certificate of Correction Sept. 19, 2006. 2. Koelle DM, Corey L. Immunological herpes simplex virus antigens and methods for use thereof. US Patent 8,852,602. October 7, 2014. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no products in development or marketed products to declare.

Publisher Copyright:
© 2016 Schiffer et al.


Dive into the research topics of 'Mathematical modeling predicts that increased hsv-2 shedding in HIV-1 infected persons is due to poor immunologic control in ganglia and genital mucosa'. Together they form a unique fingerprint.

Cite this